The neonatal period of humans is an active interval of endocrine function, especially within the hypothalamic - pituitary - testicular axis. Endocrine events during this period could potentially be disrupted by perinatal occurrences that deviate from the norm (e.g., premature delivery, birth trauma, prenatal and/or neonatal stress). Still unresolved is whether the disruption of neonatal events alters subsequent development. The current study is based on the hypothesis that the neonatal period is a second interval (in addition to the prenatal period) in early development when the central nervous system of male primates is sensitive to the organizational effects of androgen. It is further hypothesized that the chronic administration of gonadotropin releasing hormone (GnRH) analogues during the neonatal period permanently alters development of the immune system and adversely impacts on future immune function. During this past year we have continued to monitor development al changes in a group of male rhesus monkeys that were treated neonatally with a GnRH antagonist alone or in combination with androgen replacement. These animals are currently approaching full reproductive maturity. In one phase of this study we examined changes in inhibin-B and attempted to correlate these changes with FSH during development in these animals. We found that during the neonatal period inhibin-B secretion is driven by gonadotropin secretion, but during the juvenile period when gonadotropin secretion is suppressed the testes produce significant amounts of this hormone. The data also showed that in the adult rhesus monkey inhibin-B secretion varies with season, and that the reversible suppression of pituitary - testicular function during the neonatal period may permanently alter interaction between components of the hypothalamic - pituitary - testicular axis. We also examined the impact of treatment on the ability of animals to respond immunologically to foreign antige ns. Animals treated five years earlier with a GnRH antagonist exhibited altered cell-mediated and humoral-mediated immune responses to foreign agents, suggesting that the development of the immune system may have been permanently impaired by treatment. These findings deserve further study in light of evidence that the immune system of primates, including humans, produces a GnRH-like peptide, and the gene that codes for the GnRH receptor may be expressed in immune tissue. These findings have been submitted for presentation at a national scientific meeting (Society for the Study of Reproduction), and a manuscript detailing some of the above results was recently accepted for publication in the J Clin Endocr Metab. P51RR00165-36 1/1/1996 - 12/31/1996 Yerkes Regional Primate Research Center